The Role of Diet in Mast Cell Activation Syndrome (MCAS)

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This article was written on July 23, 2019, and was completely updated and reposted on May 1, 2026.

Practitioner’s Preface

Mast Cell Activation Syndrome (MCAS) is an immunological disorder in which a partial degranulation of mast cells is triggered by specific foods, heat, emotion, and physical stimuli, due to the abnormal sensitivity of mast cells, but without mast cell proliferation. MCAS is a isubtype of Mast Cell Activation Disorder (MCAD) and one of three related disorders that may occur individually or concurrently, which include Ehlers-Danlos Syndrome (hEDS), a collagen protein disorder that causes joint hypermobility and subluxation (“bendy joints”), and Postural Orthostatic Tachycardia Syndrome (POTS), a form of dysautonomia that disrupts the autonomic nervous system and results in symptoms of excessively fast heart rate (called tachycardia) as well as lightheadedness (called pre-syncope) upon standing.

In MCAS, mast cells inappropriately release excessive chemical mediators, including histamine and inflammatory cytokines, which result in chronic and recurrent severe allergy-like symptoms affecting at least two organ systems [1], and which can include facial flushing (caused by partial degranulation of mast cells), hives, abdominal pain, vomiting, diarrhea, and anaphylaxis, a severe, potentially fatal allergic reaction that involves airway constriction and a severe drop in blood pressure [2,3].

As outlined on the About Me page, in early 2019, I was diagnosed with MCAD by the head of Allergy and Immunology at a local teaching hospital in Vancouver, BC. After reading quite a few academic papers recommended by this Professor, as well as doing subsequent reading on the subject, by late 2019, I was able to help support others diagnosed with MCAS and MCAD. As my knowledge grew, in 2020, I also began supporting individuals with the related conditions of Ehlers-Danlos Syndrome (hEDS) and Postural Orthostatic Tachycardia Syndrome (POTS). I continue to keep myself current on dietary recommendations in the management of these disorders.

Mast Cell Activation Syndrome – differences in diagnostic criteria

In 2010, Akin et al. proposed the first diagnostic criteria for primary and secondary MCAS [4], followed shortly after by Mouldering & Afrin’s definition [5] in 2011. In 2012, Valent and Akin et al expanded their definition [6], and in 2021, Afrin et al established what they termed “a global consensus” criteria [7], which has been criticized by some in the field “for their lack of specificity and of supporting evidence to link such a broad range of symptoms to chronic mast cell activation” [8].

In 2022, an international consortium of leading experts in mast cell disorders formed the European Competence Network on Mastocytosis – American Initiative on Mast Cell Diseases (ECNM-AIM), and published their diagnostic criteria [9], which is the same criteria that was endorsed in 2019 by the American Academy of Allergy, Asthma and Immunology (AAAAI) [10] and which include;

(a) clinical signs of severe, recurrent, systemic mast cell activation, including in the form of anaphylaxis, and involving at least 2 organ systems, and

(b) blood test results demonstrating an increase in serum tryptase level from the individual’s baseline to 120% + 2 ng/mL or the presence of urinary histamine metabolites greater than 200% of the person’s baseline, and

(c) improvement of symptoms in response to mast cell stabilizing medications [9].

To this day, there remains a difference of opinion between Afrin’s 2021 “global consensus” criteria of MCAS [7] and the 2022 diagnostic criteria of the ECNM-AIM [9].

Mast Cell Degranulation

As outlined in a 2023 paper by Molderings and Afrin, mast cells will only occasionally release their pre-stored mediators via a classic whole mast cell degranulation, resulting in anaphylaxis [3]. Thankfully, this is the exception, rather than the rule (otherwise, anaphylaxis would occur every time mast cells were activated, which is not the case [3]). Rather than wholly degranulate, mast cells usually selectively release the content of individual secretory granules of histamine or individual mediators, including specific inflammatory cytokines, without whole mast cell degranulation.

What is Histamine?

Most people recognize the term “antihistamine” in the context of seasonal allergies, but histamine itself performs many helpful functions, such as stimulating stomach acid production. In the immune system, histamine acts as a defense mechanism. When the body perceives a threat, mast cells release histamine, causing inflammation to signal the immune system to respond. However, in MCAS and MCAD, histamine either isn’t broken down properly or is released inappropriately when no actual allergen is present.

Histamine is normally rapidly degraded by two enzymes: diamine oxidase (DAO), which works primarily in the digestive tract, and histamine-N-methyltransferase (HNMT), which deactivates histamine at the receptor level throughout various body tissues. If these enzymes are dysfunctional, histamine accumulates.

Histamine intolerance is often compared to an overflowing “bucket” where the body can handle small amounts of histamine spread out over time, but the mast cells overflow, or degranulate, when there is more histamine than the body can degrade and deactivate.

Dietary management of MCAS often involves helping an individual learn how to limit the amount of histamine-producing and histamine-releasing foods that they are eating at a time, and throughout the day.

Gastrointestinal (GI) Symptoms of Mast Cell Activation

Gastrointestinal (GI) symptoms of uncomplicated MCAS, where there is no concurrent presence of either Ehlers-Danlos Syndrome (hEDS) or Postural Orthostatic Tachycardia Syndrome (POTS), can include abdominal pain, vomiting, and/or diarrhea, however most individuals who have come to me for dietary support with MCAS over the years have also been diagnosed with hEDS and or POTS. As outlined below, a study with ~140 people with MCAS found that <40% of those with MCAS did not also have hEDS and/or POTS.

Clinical Applications

Dietary management of uncomplicated MCAS, where there is no concurrent presence of either Ehlers-Danlos Syndrome (hEDS) or Postural Orthostatic Tachycardia Syndrome (POTS), often involves helping an individual learn to limit both the amount of histamine-producing and histamine-releasing foods that they eat at a time, and also the overall amount they eat throughout the day.

The clinical reality is that, in a 2019 study of 139 people who were diagnosed with MCAS and who had GI symptoms that did not respond to standard treatment, only 36 people had uncomplicated MCAS [11].

  • 23.7% were also diagnosed with hEDS
  • 25.2% were also diagnosed with POTS
  • 15.1% were diagnosed with both hEDS and POTS [11]

As outlined in the recent article titled Treating GI Symptoms in Postural Orthostatic Tachycardia Syndrome (POTS), dietary support for someone with both MCAS and POTS needs to include the fluid and sodium intake recommendations for POTS, and would also need to factor in dietary modifications for gut dysmotility issues that are often present.

If the individual also has hEDS, as outlined in the article, Dietary Support for Hypermobile Ehlers-Danlos Syndrome (hEDS), dietary modifications could range from a low fermentable carbohydrate diet, dairy-free or gluten-free diet, or could be significantly more complex, involving implementing a specialized diet for gastroparesis.

Since more than half of the time, MCAS presents with one or both of the other disorders in the “trifecta” of MCAS, hEDS, and POTS, dietary support necessarily has to be evaluated on a case-by-case basis. For this reason, the first step to getting started with services is with an Initial Consultation, which will enable us to meet to discuss your specific diagnoses, any diagnostic tests that are still ongoing, your specific symptoms, as well as your priority in addressing them. 

More Info?

If you have been diagnosed with any one of the “trifecta” of Mast Cell Activation Syndrome (MCAS) with or without Ehlers-Danlos Syndrome (hEDS), and/or Postural Orthostatic Tachycardia Syndrome (POTS), I can help you minimize your symptoms. Learn about me and view my services for hEDS, MCAS, and POTS page.

To your good health!

Joy

You can follow me on:

Twitter: https://twitter.com/jyerdile
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References

  1. Valent P, Hartmann K, Bonadonna P, Gulen T, Brockow K, Alvarez-Twose I, et al. Global classification of mast cell activation disorders: an ICD-10-CM-adjusted proposal of the ECNM-AIM consortium. J Allergy Clin Immunol Pract. 2022;10(8):1941–50.
  2. Aziz Q, Harris L, Goodman B. AGA Clinical Practice Update on GI Manifestations and Autonomic or Immune Dysfunction in Hypermobile Ehlers-Danlos Syndrome: Expert Review, Clinical Gastroenterology and Hepatology, 2025; 23, 1291-1302
  3. Molderings, G.J., Afrin, L.B. A survey of the currently known mast cell mediators with potential relevance for therapy of mast cell-induced symptoms. Naunyn-Schmiedeberg’s Arch Pharmacol 396, 2881–2891 (2023). https://doi.org/10.1007/s00210-023-02545-y
  4. Akin C, Valent P, Metcalfe DD. Mast cell activation syndrome: proposed diagnostic criteria. J Allergy Clin Immunol. 2010;126(6):1099-104 e4.
  5. Molderings, G.J et al, Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options. J. Hematol Oncol 2011;4:10
  6. Valent P, Akin C, Arock M, Brockow K, Butterfield JH, Carter MC, et al. Definitions, criteria, and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch
    Allergy Immunol. 2012;157(3):215–25.
  7. Afrin LB, Ackerley MB, Bluestein LS, Brewer JH, Brook JB, Buchanan AD, et al. Diagnosis of mast cell activation syndrome: a global “consensus-2.” Diagnosis (Berl). 2021;8(2):137–52.
  8. Lee, E., Picard, M. Diagnosis and management of mast cell activation syndrome (MCAS) in Canada: a practical approach. Allergy Asthma Clin Immunol 21, 49 (2025). https://doi.org/10.1186/s13223-025-00998-9
  9. Valent P, Hartmann K, Bonadonna P, Gulen T, Brockow K, Alvarez-Twose I, et al. Global classification of mast cell activation disorders: an ICD-10-CM-adjusted proposal of the ECNM-AIM consortium. J Allergy Clin Immunol Pract. 2022;10(8):1941–50.
  10. Weiler CR, Austen KF, Akin C, Barkoff MS, Bernstein JA, Bonadonna P, et al. AAAAI mast cell disorders committee work group report: mast cell activation syndrome (MCAS) diagnosis and management. J Allergy Clin Immunol.
    2019;144(4):883–96.
  11. Weinstock LB, Brook J, Kaleem Z, et al. 1194 Small intestinal bacterial overgrowth is common in mast cell activation syndrome. Am J Gastroenterol 2019;114:S671.
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